Over the past two years the NIA-Late-Onset Alzheimer's Disease (NIA-LOAD) Study was developed for the recruitment of individuals from families with late onset familial Alzheimer's disease and supported through supplements to 18 Alzheimer's Disease Centers. This group, led by a Genetics Coordinating Core (GCC) at Columbia University has developed, circulated and refined a procedures manual and has overseen the collection of 1,885 samples from 422 families for which data has been transmitted to the National Cell Repository for Alzheimer's Disease (NCRAD) located at Indiana University. The intent of this Resource-Related Research Project-Cooperative Agreement is to complete the collection of new families, recruit appropriate members in existing families and initiate and complete follow-up in all participating families. Five of the original Centers (Columbia University, Indiana University, Mayo Clinic, University of Washington and Washington University) will form a consortium with the existing GCC at Columbia University and will also coordinate follow-up of existing families through small targeted subcontracts with the remaining 13 Centers. The aims of this proposal are to: l)Complete the current collection of 1,000 families;2) Identify newly affected family members and appropriate unaffected members by expanding pedigrees in participating families;3) Develop and implement standardized follow-up procedures for the participating families and family members;4) Improve statistical power of the sample for genetic linkage analysis by implementing methods for standardized assessment of a series of quantitative traits at the time of follow-up for all families;5) Complete the recruitment and begin follow-up of 1,000 individuals unrelated to the participating families without dementia to form a "control" group;6) Apply to the Center for Inherited Disease Research to have genotyping completed in the first 500 families. At the conclusion of this five year proposal we will have created a rich resource of 1,000 well-characterized families with late-onset, familial Alzheimer's disease, which is essential for the success of genetics research in this area. The NIA-LOAD Study has added specific criteria for the inclusion of families with late-onset disease and has used standardized methods to identify affected and unaffected individuals across Centers. This collection of families will be complimented by a similar number of unrelated controls. The need for additional, well characterized families is essential for identifying the remaining genetic variants and role in the disease. This application proposes to work with the network of NIA supported Alzheimer's Disease Centers to provide the resources critical to Alzheimer's disease researchers that will allow the elucidation of susceptibility genes. BACKGROUND, SIGNIFICANCE, AND INNOVATION